Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth
Authors: Barrett M. Welch, Alexander P. Keil, Jessie P. Buckley, Antonia M. Calafat, Kate E. Christenbury, Stephanie M. Engel, Katie M. O'Brien, Emma M. Rosen, Tamarra James-Todd, Ami R. Zota, Kelly K. Ferguson, Akram N. Alshawabkeh, José F. Cordero, John D. Meeker, Emily S. Barrett, Nicole R. Bush, Ruby H. N. Nguyen, Sheela Sathyanarayana, Shanna H Swan, David E. Cantonwine, Thomas F. McElrath, Jenny Aalborg, Dana Dabelea, Anne P. Starling, Russ Hauser, Carmen Messerlian, Yu Zhang, Asa Bradman, Brenda Eskenazi, Kim G. Harley, Nina Holland, Michael S. Bloom, Roger B. Newman, Abby G. Wenzel, Joseph M. Braun, Bruce P. Lanphear, Kimberly Yolton, Pam Factor-Litvak, Julie B. Herbstman, Virginia A. Rauh, Erma Z. Drobnis, Amy E. Sparks, J. Bruce Redmon, Christina Wang, Alexandra M. Binder, Karin B. Michels, Donna D. Baird, Anne Marie Z. Jukic, Clarice R. Weinberg, Allen J. Wilcox, David Q. Rich, Barry Weinberger, Vasantha Padmanabhan, Deborah J. Watkins, Irva Hertz-Picciotto, Rebecca J. Schmidt
Journal: JAMA Pediatrics (2022)

Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.